The overall objective of this research is to determine how carcinogenic polycyclic aromatic hydrocarbons bind to DNA in cell cultures from different species and the relationship of this binding to the induction of biological effects. This will be accomplished by analyzing the hydrocarbon-DNA interaction products formed in cell cultures from several species by both immobilized boronate chromatography and high-pressure liquid chromatography to determine the nature of the adducts formed and the relative persistence of specific adducts. Identification of the structures of the hydrocarbon-DNA adducts will be carried out directly by the application of mass spectrometric techniques as well as by radioisotope studies involving hydrolysis and chromatography. Based upon the types of hydrocarbon-DNA adducts formed, cells from various species will be selected for use as activators in mammalian cell-mediated mutation assays. The V79 target cells will be separated from the activator cells by an immunoseparation procedure and the hydrocarbon-DNA adducts formed in the target cells will be analyzed. The relationship of the formation of specific hydrocarbon-DNA adducts to the induction of mutation and cytotoxicity will be investigated. The carcinogenic hydrocarbons to be studied include both the unsubstitutedd hydrocarbon benzo(a)pyrene and the methyl-substituted, extremely potent carcinogen 7, 12-dimethylbenz(a)anthracene. At present very little is known about the role of specific 7,12-dimethylbenz(a)anthracene-DNA adducts in the induction of biological effects. The proposed studies will determine how these hydrocarbons interact with DNA, how these interactions vary in cells from different species and how specific types of hydrocarbon-DNA interactions are related to the induction of biological effects. This information will help to establish which types of hydrocarbon-DNA interactions are important for carcinogenesis and what characteristics would make a cell, tissue or species susceptible to these types of hydrocarbon-DNA interactions.